E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pertussis infection |
Kinkhoest infectie |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess magnitude and changes in pertussis toxin (PT) specific IgG antibody levels just before (T0) and 28 days (T4) after the booster vaccination in 2 cohorts of children (7-10 and 11-15 years of age), 1 cohort of young adults (20-34 years of age) and 1 cohort of elderly (60-70 years of age) in three different countries. |
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E.2.2 | Secondary objectives of the trial |
• Assess the PT specific IgG antibody levels 1 year (T5) after vaccination.
• Assess the specific IgG antibody levels against other pertussis vaccine antigens (e.g. FHA, Prn and Fim2,3), as well as non-pertussis vaccine antigens (e.g. diphtheria toxoid, tetanus toxoid) at T0, T4 and T5.
• Determine pertussis-specific IgG-subclasses and -avidity at T0, T4 and T5.
• Determine functional pertussis-specific antibody levels at T0, T4 and T5.
• Assess magnitude and longevity of memory B cell responses against the various B. pertussis vaccine proteins at T0, 7 days post vaccination (T2), T4 and T5, to determine the effects of an aP booster vaccination in children, young adults and elderly on memory and effector cell populations.
• Compare pertussis antigen-specific T helper responses and their ratio’s at T0, 14 days post vaccination (T3), T4 and T5.
• Collection and biobanking of biological samples for identifying biomarkers of lasting memory or waning of immunity to Pertussis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• normal general health;
• within the right age group for the cohort;
• received all regular vaccines for their age group according to the Dutch NIP, UK NIP or Finnish NIP; a copy of the vaccination booklet will be included in the participant’s documents. If booklet is not available for cohorts A, B and C, vaccination status will be checked with regulatory agencies / GP. For cohort D this booklet might not be available due to their age;
• provision of written informed consent (see section 11.2 for details);
• willing to adhere to the protocol and be available during the study period.
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E.4 | Principal exclusion criteria |
• present evidence of serious disease(s) within the last 3 months before inclusion requiring immunosuppressive or immune modulating medical treatment, such as systemic corticosteroids, that might interfere with the results of the study ;
• chronic infection
• known or suspected immune deficiency;
• history of any neurologic disorder, including epilepsy;
• previous administration of serum products (including immunoglobulins) within 6 months before vaccination and blood sampling;
• known or suspected allergy to any of the vaccine components (by medical history);
• occurrence of serious adverse events (SAEs) after primary DTwP-IPV vaccination, DTaP-IPV vaccination or any other vaccination (by medical history);
• vaccination with any other pertussis vaccine than those described in the inclusion criteria (i.e. only according to NIP);
• vaccination with any other DT-IPV vaccine in the last 5 years, DT-IPV vaccination according to NIP in cohort B is no exclusion;
• children between 8 and 10 years of age eligible for cohort A in the Netherlands who have already received the diphtheria and tetanus toxoid vaccine (DT)-IPV booster vaccination according to the Dutch NIP around 9 years of age;
• mixed wP and aP priming within a participant, cohort B;
• Pregnancy |
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E.5 End points |
E.5.1 | Primary end point(s) |
Anti-PT specific IgG-antibodies in serum and their avidity will be determined for all samples in a PERISCOPE serological core assay, comparing T0, T4 and T5. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
before vaccination (T0)
1 month after vaccination (T4)
1 year after vaccination (T5) |
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E.5.2 | Secondary end point(s) |
-Specific IgG-levels to other pertussis vaccine antigens (FHA; Prn and Fim2,3), as well as to non-pertussis antigens (diphtheria toxoid and tetanus toxoid) will be determined at T0, T4 and T5, using a PERISCOPE serological multiplex immunoassay.
-Functional pertussis-specific antibody levels will be determined in serum samples at T0, T4 and T5, using PERISCOPE core assays as described in section 8.3.4. Differences in levels of functional antibodies will be measured before and after vaccination. Functional antibody assays include bacterial adherence inhibition (BAI), PT neutralisation (PTNA), serum bactericidal activity (SBA), and bacterial opsonophagocytosis assay (OPA). Other serological parameters such as avidity, subclass distribution (IgA, IgM) are optional in serum samples .
-Antigen-specific memory B cell responses at time points T0, T2, T4 and T5 will be measured to determine the effects of aP booster vaccination in children, young adults and elderly, using PERISCOPE B cell core assay.
-Characterisation of the effect of an aP booster on the specific T cell immune response, both early after the boost and later on, in different age groups, vaccinated initially either with a whole cell or an acellular vaccine.
-Collection and biobanking of biological samples to be used for testing in novel exploratory immunoassays and for possible bridging to other pertussis vaccine studies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
before vaccination (T0)
1 day after vaccination (T1)
7 days after vaccination (T2)
14 days after vaccination (T3)
1 month after vaccination (T4)
1 year after vaccination (T5) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
longitudinal intervention study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |